Hepatocellular cancer (HCC) is the 5th most common cancer in the world, and has become more common with the increased incidence of hepatitis C. Transcatheter chemoembolization (TACE) has become the standard treatment for patients with unresectable HCC, despite the lack of evidence demonstrating the superiority of TACE compared to embolization without chemotherapy. There are financial and toxicity concerns associated with the use of chemotherapy that make it important to define the best method of arterial emboliztion for HCC. A microscopic bead has been developed that can be loaded with doxorubicin and used for hepatic arterial embolization, resulting in high prolonged concentration of drug within the tumor. To assess the role of doxorubicin in hepatic arterial embolization of HCC, we will conduct the first randomized trial to determine the difference in response to treatment, time to progression and overall survival using a plain bead versus the bead loaded with 150 mg of doxorubicin. In Aim 1 we propose to characterize the radiologic response to treatment as manifest by change in viable tumor on contrast enhanced CT scans. Aim 2 is designed to validate an automated CT volumetric method of assessing tumor necrosis, and correlate this method with conventional means of assessing response to treatment. Aim 3 will establish whether use of the drug eluting bead increases the time to progression or survival, and whether response to treatment, as estimated by development of tumor necrosis on the initial post-treatment CT scans, can be used as a surrogate biomarker for outcome. This study is important because it will provide objective data regarding the role of doxorubicin in hepatic arterial embolization, and justification for the increased cost of the embolic agent. What we learn about toxicity will likely change the way that chemotherapeutic agents are administered transarterially, not just for HCC but for any hypervascular liver tumor. Targeting chemotherapy to liver tumors has the potential to have a significant impact on clinical outcome, and may improve the overall survival of patients for whom there is no other recognized treatment. The validation of a new imaging method of assessing response to treatment that might replace current less sensitive methods is important for all cancer patients and cancer investigators The incidence of hepatocellular carcinoma (HCC) in the United States is increasing. The vast majorities of patients are not operative candidates at the time of diagnosis, and are treated with hepatic arterial therapies. Controversy exists regarding the need to use chemotherapeutic agents for intra-arterial treatment. The use of chemotherapy adds not only expense, but potential toxicity. This study is designed to determine the incremental value of arterial chemotherapy, as well as to validate an automated imaging method of assessing response to treatment. [unreadable] [unreadable] [unreadable]